α-Acetal, ω-alkyne poly(ethylene oxide) was synthesized as building block of glycoconjugated poly(ε-caprolactone)-graft-poly(ethylene oxide) (PCL-g-PEO) copolymers. The alkyne group is indeed instrumental for the PEGylation of a poly(α-azido-ε-caprolactone-co-ε-caprolactone) copolymer by the Huisgen’s 1,3 dipolar cycloaddition, i.e., a click reaction. Moreover, deprotection of the acetal end-group of the hydrophilic PEO grafts followed by reductive amination of the accordingly formed aldehyde with an aminated sugar is a valuable strategy of glycoconjugation of the graft copolymer, whose micelles are then potential. A model molecule (fluoresceinamine) was first considered in order to optimize the experimental conditions for the reductive amination. These conditions were then extended to the decoration of the graft copolymer micelles with mannose, which is a targeting agent of dendritic cells and macrophages. The bioavailability of the sugar units at the surface of micelles was investigated by surface plasmon resonance (SPR). The same question was addressed to nanoparticles stabilized by the graft copolymer. Enzyme linked lectin assay (ELLA) confirmed the availability of mannose at the nanoparticle surface. [less ▲]

This paper aims at reporting the end-functionalization of a PEO block of an amphiphilic α-acetal-PEO-b-PCL copolymer. The acetal end-group, which is the fragment of the initiator used in the EO ... [more ▼]

This paper aims at reporting the end-functionalization of a PEO block of an amphiphilic α-acetal-PEO-b-PCL copolymer. The acetal end-group, which is the fragment of the initiator used in the EO polymerization, was first hydrolyzed into an aldehyde that was then reacted with an amine by reductive amination reaction in water. This two-step derivatization was carried out in one pot. In a preliminary study a model amine, i.e. fluorescein amine, was used and the impact of the composition, thus of the Hydrophilic–Lipophilic Balance (HLB) of the amphiphilic copolymer, was studied. The experimental conditions were extended to the coupling of an aminated mannose to the diblock copolymer. The frozen micelles formed by the mannosylated copolymer proved to form complexes with various lectins as shown by Surface Plasmon Resonance (SPR) and Isothermal Titration Calorimetry (ITC). [less ▲]

Poly(lactide-co-glycolide) (PLGA) is extensively used in pharmaceutical applications, for example, in targeted drug delivery, because of biocompatibility and degradation rate, which is easily tuned by the ... [more ▼]

Poly(lactide-co-glycolide) (PLGA) is extensively used in pharmaceutical applications, for example, in targeted drug delivery, because of biocompatibility and degradation rate, which is easily tuned by the copolymer composition. Nevertheless, synthesis of sugar-labeled amphiphilic copolymers with a PLGA backbone is quite a challenge because of high sensitivity to hydrolytic degradation. This Article reports on the synthesis of a new amphiphilic copolymer of PLGA grafted by mannosylated poly(ethylene oxide) (PEO). A novel building block, that is, α-methoxy-ω-alkyne PEO-clip-N-hydroxysuccinimide (NHS) ester, was prepared on purpose by photoreaction of a diazirine containing molecular clip. This PEO block was mannosylated by reaction of the NHS ester groups with an aminated sugar, that is, 2-aminoethyl-α-d-mannopyroside. Then, the alkyne ω-end-group of PEO was involved in a copper alkyne- azide coupling (CuAAC) with the pendent azides of the aliphatic copolyester. The targeted mannose-labeled poly(lactide-co-glycolide-co-ε-caprolactone)-graft-poly(ethylene oxide) copolymer was accordingly formed. Copolymerization of d,l-lactide and glycolide with α-chloro-ε-caprolactone, followed by substitution of chlorides by azides provided the azido-functional PLGA backbone. Finally, micelles of the amphiphilic mannosylated graft copolymer were prepared in water, and their interaction with Concanavalin A (ConA), a glyco-receptor protein, was studied by quartz crystal microbalance. This study concluded to the prospect of using this novel bioconjugate in targeted drug delivery. [less ▲]

Diabetes is a disorder of glucose regulation, characterized by an accumulation of glucose in the blood. The breakdown of glucose regulation can be attributed to the pancreas’s inability to secrete insulin ... [more ▼]

Diabetes is a disorder of glucose regulation, characterized by an accumulation of glucose in the blood. The breakdown of glucose regulation can be attributed to the pancreas’s inability to secrete insulin or to the body’s inability to properly use it. The usual treatment for type 1 diabetes consists in multiple subcutaneous insulin injections, daily administered using needles, insulin pen or insulin pump. However, this method doesn’t maintain normoglycemia and can lead to complications such as limb amputation, blindness, and kidney failure. To avoid such abnormal episodes, scientists imagined smart systems which are able to regulate the glucose level by themselves. During the past decades, a large variety of micro- and nanocarriers have been developed in order to improve efficiency, availability and toxicity profiles of drugs. In this field, stimuli-responsive polymer multilayers have attracted great scientific interest because of their potential applications as controlled delivery or release systems, for chemicals and drugs. A category of stimuli-responsive materials is able to sense glucose and respond to it by a modification of their porosity, leading to a release of insulin. The objective of this work was to investigate the formation of glucose responsive hollow microcapsules (5 microns) made of polyelectrolyte copolymers. These copolymers are composed of carbohydrate-sensitive functions, such as boronic acid and diols (PVOH), known for forming reversible covalent ether bond. In presence of carbohydrates such as glucose, the ether bonds will be reversibly broken and, consequently, the porosity of the glucose particles will change. Therefore, polyelectrolyte copolymers were synthesized by control radical polymerization, i.e. reversible addition-fragmentation chain transfer (RAFT, polyboronic acid) and cobalt-mediated radical polymerization (CMRP, PVOH). Using these polyelectrolytes as polyanions and poly(allylamine) (PAH) as a polycation, we undertook the formation of layer-by-layer capsules starting with a template of CaCO3microparticles which can be dissolved with EDTA leading to the formation of hollow microcapsules. Bovin serum albumin isothiocyanate (BSA-FITC) was used to fill the CaCO3microparticles and to determine the porosity of the resulting capsules in function of the glucose concentration. The sugar-dependent porosity is investigated by following the release of encapsulated BSA-FITC by spectro-fluoroscopy. [less ▲]

A new type of multilayer capsules is designed for use as antibacterial vehicles by taking advantage of the properties of natural polysaccharides. These capsules, prepared by layer-by-layer assembly of ... [more ▼]

A new type of multilayer capsules is designed for use as antibacterial vehicles by taking advantage of the properties of natural polysaccharides. These capsules, prepared by layer-by-layer assembly of hyaluronic acid (HA; see graphic) and quaternized chitosan (QCHI) derivatives onto sacrificial colloidal particles, show distinct killing activities depending on the nature of the polysaccharide on the surface. [less ▲]

Functionalized poly-ε-caprolactone-block-polyethyleneglycol (PCL-PEG) amphiphilic copolymers were prepared to be constituents of nanocarriers used for the targeting of specific cells. Hence, we conceived ... [more ▼]

Functionalized poly-ε-caprolactone-block-polyethyleneglycol (PCL-PEG) amphiphilic copolymers were prepared to be constituents of nanocarriers used for the targeting of specific cells. Hence, we conceived a smooth and simple photografting methodology on these copolymers using a bifunctional molecular clip (O-succinimidyl-4-(p-azido-phenyl)butanoate). We prepared PCL-PEGs with pendent N-hydroxysuccinimide esters and studied the grafting with 3H-lysine, which radioactivity was counted by LSC. Several parameters were investigated, such as behavior of homopolymers, initial concentrations, irradiation, and incubation durations. Evidences of a “PEG directed photografting” are discussed and this selectivity could be improved by a selective solvent technique. The photografting on different PCL-PEGs revealed a dependency of the rates to the crystallinity of the copolymers. Several controls by SEC, DLS, and TEM of the treated copolymers were realized. Lastly, the coupling of α-d-mannopyranoside ligand was performed, reaching amounts of 5400 nmol/g of PCL-PEG. This derivatized PCL-PEG enters in the preparation of nanocarriers used for the targeting of antigen presenting cells. [less ▲]

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the ... [more ▼]

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the surface functionalization of poly(d,l-lactic acid) (PLA) nanoparticles by mannose moieties: It consists in using an amphiphilic mannosylated poly(ethylene oxide)-b-poly(-caprolactone) (PEO-b-PCL) diblock copolymer as a bioresorbable surface modifier in a simple nanoprecipitation-evaporation procedure. The size and zeta potential of the nanoparticles were found to depend on the molar copolymer/PLA ratio, demonstrating the influence of the copolymer on the formation of the nanoparticles. The bioavailability of the mannose residues as specific recognition sites on the nanoparticle surface could be demonstrated by a modified enzyme-linked lectin assay (ELLA) using biotin-labeled lectins which interact specifically with α-d-mannopyrannoside derivatives. Besides specific interaction by lectin−mannose complex formation, nonspecific adsorption of the proteins on the nanoparticle surface was observed. These results were fully supported by isothermal titration calorimetry experiments which suggested that the balance between specific and nonspecific interactions can be controlled by the amount of glycosylated polymer used for the preparation of the nanoparticles. Such nanoparticles are expected to be specifically recognized by mannose receptors, which are highly expressed in cells of the immune system. The targeting properties of these carrier systems combined with their potential adjuvant effects due to their size in the range of 200−300 nm make them attractive candidates as vaccine delivery systems. [less ▲]

A novel bioeliminable amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) diblock copolymer end-capped by a mannose residue was synthesized by sequential controlled polymerization of ethylene oxide and epsilon-caprolactone, followed by the coupling of a reactive mannose derivative to the PEO chain end. The anionic polymerization of ethylene oxide was first initiated by potassium 2-dimethylaminoethanolate. The ring-opening polymerization of epsilon-caprolactone was then initiated by the omega-hydroxy end-group of PEO previously converted into an Al alkoxide. Finally, the saccharidic end-group was attached by quaternization of the tertiary amine (alpha-end-group of the PEO-b-PCL with a brominated mannose derivative. The copolymer was fully characterized in terms of chemical composition and purity by high-resolution NMR spectroscopy and size exclusion chromatography. Furthermore, measurements with a pendant drop tensiometer showed that both the mannosylated copolymer and the non-mannosylated counterpart significantly decreased the dichloromethane/water interfacial tension. Moreover, these amphiphilic copolymers formed monodisperse spherical micelles in water with an average diameter of similar to 11 nin as measured by dynamic light scattering and cryo-transmission electron microscopy. The availability of mannose as a specific recognition site at the surface of the micelles was proved by isothermal titration microcalorimetry (ITC), using the BclA lectin (from Burkholderia cenocepacia), which interacts selectively with a-D-mannopyranoside derivatives. The thermodynamic parameters of the lectin/mannose interaction were extracted from the ITC data. These colloidal systems have great potential for drug targeting and vaccine delivery systems. [less ▲]